Effects of Spinal Cord Stimulation on Gait in Patients With Parkinson´s Disease

NCT ID: NCT05148468

Last Updated: 2024-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-30

Study Completion Date

2024-03-01

Brief Summary

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Spinal cord stimulation (SCS) for Parkinson´s disease (PD) has been studied for a decade but consensus on efficacy is still lacking, with the previous stimulation standard paresthesia inducing threshold hampering adequate subject blinding. Considering that tonic stimulation for pain has been shown to be efficacious for most patients on subthreshold stimulation parameters we hypothesize a similar result with it´s use on PD. The investigators aim to:

1. Produce stronger evidence on SCS efficacy for PD in regards to gait, motor scores and quality of life measures by incorporating subthreshold in a randomized cross over placebo-controlled study with a large sample.
2. Identify predictors of good response to SCS therapy by performing trans spinal magnetic stimulation (TSMS) before SCS implant and correlating the response to SCS to that of the noninvasive TSMS.
3. Better provide biomarkers of SCS therapy through functional magnetic resonance imaging and electroencephalographic mapping.

Detailed Description

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Gait impairment in Parkinson´s Disease (PD) is often refractory to standard medication therapy and functional surgery options currently explored resulting in grave loss of independence and quality of life. Spinal cord stimulation (SCS) has been explored for its role in PD after enthusiastic animal studies and despite mixed initial results is currently a very promising candidate for ameliorating hard to treat gait and balance disorders.

Consensus on tonic SCS efficacy is hampered mostly due to small samples and lack of randomized controlled trials so far, and the impossibility of subject blinding due to standard stimulation settings using currents over the paresthesia inducing threshold. Some small studies already attempted subthreshold blinding and all resulted in non significant results, however with no important difference when switching to suprathreshold settings, thus raising the possibility of non responder subjects or inefficient therapy and calling for additional exploration. The investigators aim to explore the feasibility of a placebo controlled trial using subthreshold stimulation with a larger sample and produce stronger evidence on SCS efficacy for PD.

Additionally, the possibility of non responder subjects will be explored by correlating the degree of response to SCS to patient demographic characteristics including age, PD severity and cognition, gait characteristics and the degree of response to trans spinal magnetic stimulation (TSMS), a non invasive magnetic stimulation of upper thoracic spinal region, aiming to identify prognostic factors for the therapy.

Finally, functional magnetic resonance imaging and electroencephalographic mapping will be performed in order to identify biomarkers of SCS therapy.

Conditions

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Parkinson Disease Gait Disorders, Neurologic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Double blinded randomized placebo controlled cross over study
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Patients and examiners will be blinded to stimulation status

Study Groups

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Active stimulation

During active stimulation phase, patients will receive through the spinal cord stimulator active tonic stimulation with amplitude set to 90% of paresthesia inducing threshold, therefore allowing blinding. Patients will be evaluated after a three week wash out period with no stimulation and after three weeks of continuous active stimulation.

Group Type EXPERIMENTAL

Active spinal cord stimulation

Intervention Type DEVICE

Spinal cord stimulation is accomplished with surgically implanted epidural leads at Th3 - Th4 levels and a pulse generator implanted in subcutaneous fat. During active stimulation amplitude will be set to 90% paresthesia inducing threshold.

Sham stimulation

During sham stimulation phase, patients will receive through the spinal cord stimulator a zero amplitude stimulation, therefore having no electrical current passing through epidural leads but with the program status still displayed as "on" if checked with patient's personal controller. Patients will be evaluated after a three week wash out period with no stimulation and after three weeks of continuous sham stimulation.

Group Type SHAM_COMPARATOR

Sham spinal cord stimulation

Intervention Type DEVICE

Spinal cord stimulation is accomplished with surgically implanted epidural leads at Th3 - Th4 levels and a pulse generator implanted in subcutaneous fat. During sham stimulation amplitude will be set to zero.

Interventions

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Active spinal cord stimulation

Spinal cord stimulation is accomplished with surgically implanted epidural leads at Th3 - Th4 levels and a pulse generator implanted in subcutaneous fat. During active stimulation amplitude will be set to 90% paresthesia inducing threshold.

Intervention Type DEVICE

Sham spinal cord stimulation

Spinal cord stimulation is accomplished with surgically implanted epidural leads at Th3 - Th4 levels and a pulse generator implanted in subcutaneous fat. During sham stimulation amplitude will be set to zero.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Diagnosed Parkinson´s Disease with Hoehn Yahr scale between 2,5 and 4,0
* Main complaint of balance or freezing of gait
* Score of 2 or more on subitem 3.11 of the MDS UPDRS scale concerning Freezing of Gait severity.
* Capable of informed consent

Exclusion Criteria

* Frequent lower limb, lower back or hip pain scoring 3 or more on visual analog scale
* Uncontrolled or serious comorbidities such as uncontrolled diabetes mellitus, renal disease, anticoagulation, immunosuppression or other medical conditions that present a contraindication for SCS surgery
* Psychosis, uncontrolled depression (BDI \>14) or anxiety disorder (BAI \>14)
Minimum Eligible Age

21 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Sao Paulo General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital das Clínicas da Faculdade de Medicina da USP

São Paulo, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Agari T, Date I. Spinal cord stimulation for the treatment of abnormal posture and gait disorder in patients with Parkinson's disease. Neurol Med Chir (Tokyo). 2012;52(7):470-4. doi: 10.2176/nmc.52.470.

Reference Type BACKGROUND
PMID: 22850494 (View on PubMed)

Fuentes R, Petersson P, Nicolelis MA. Restoration of locomotive function in Parkinson's disease by spinal cord stimulation: mechanistic approach. Eur J Neurosci. 2010 Oct;32(7):1100-8. doi: 10.1111/j.1460-9568.2010.07417.x.

Reference Type BACKGROUND
PMID: 21039949 (View on PubMed)

de Andrade EM, Ghilardi MG, Cury RG, Barbosa ER, Fuentes R, Teixeira MJ, Fonoff ET. Spinal cord stimulation for Parkinson's disease: a systematic review. Neurosurg Rev. 2016 Jan;39(1):27-35; discussion 35. doi: 10.1007/s10143-015-0651-1. Epub 2015 Jul 30.

Reference Type BACKGROUND
PMID: 26219854 (View on PubMed)

Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA. Spinal cord stimulation restores locomotion in animal models of Parkinson's disease. Science. 2009 Mar 20;323(5921):1578-82. doi: 10.1126/science.1164901.

Reference Type BACKGROUND
PMID: 19299613 (View on PubMed)

Thevathasan W, Mazzone P, Jha A, Djamshidian A, Dileone M, Di Lazzaro V, Brown P. Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease. Neurology. 2010 Apr 20;74(16):1325-7. doi: 10.1212/WNL.0b013e3181d9ed58. No abstract available.

Reference Type BACKGROUND
PMID: 20404313 (View on PubMed)

Fenelon G, Goujon C, Gurruchaga JM, Cesaro P, Jarraya B, Palfi S, Lefaucheur JP. Spinal cord stimulation for chronic pain improved motor function in a patient with Parkinson's disease. Parkinsonism Relat Disord. 2012 Feb;18(2):213-4. doi: 10.1016/j.parkreldis.2011.07.015. Epub 2011 Aug 23. No abstract available.

Reference Type BACKGROUND
PMID: 21865071 (View on PubMed)

Santana MB, Halje P, Simplicio H, Richter U, Freire MAM, Petersson P, Fuentes R, Nicolelis MAL. Spinal cord stimulation alleviates motor deficits in a primate model of Parkinson disease. Neuron. 2014 Nov 19;84(4):716-722. doi: 10.1016/j.neuron.2014.08.061. Epub 2014 Oct 30.

Reference Type BACKGROUND
PMID: 25447740 (View on PubMed)

Pinto de Souza C, Hamani C, Oliveira Souza C, Lopez Contreras WO, Dos Santos Ghilardi MG, Cury RG, Reis Barbosa E, Jacobsen Teixeira M, Talamoni Fonoff E. Spinal cord stimulation improves gait in patients with Parkinson's disease previously treated with deep brain stimulation. Mov Disord. 2017 Feb;32(2):278-282. doi: 10.1002/mds.26850. Epub 2016 Nov 10.

Reference Type BACKGROUND
PMID: 27862267 (View on PubMed)

Akiyama H, Nukui S, Akamatu M, Hasegawa Y, Nishikido O, Inoue S. Effectiveness of spinal cord stimulation for painful camptocormia with Pisa syndrome in Parkinson's disease: a case report. BMC Neurol. 2017 Aug 3;17(1):148. doi: 10.1186/s12883-017-0926-y.

Reference Type BACKGROUND
PMID: 28774283 (View on PubMed)

Samotus O, Parrent A, Jog M. Spinal Cord Stimulation Therapy for Gait Dysfunction in Advanced Parkinson's Disease Patients. Mov Disord. 2018 May;33(5):783-792. doi: 10.1002/mds.27299. Epub 2018 Feb 14.

Reference Type BACKGROUND
PMID: 29442369 (View on PubMed)

de Lima-Pardini AC, Coelho DB, Souza CP, Souza CO, Ghilardi MGDS, Garcia T, Voos M, Milosevic M, Hamani C, Teixeira LA, Fonoff ET. Effects of spinal cord stimulation on postural control in Parkinson's disease patients with freezing of gait. Elife. 2018 Aug 2;7:e37727. doi: 10.7554/eLife.37727.

Reference Type BACKGROUND
PMID: 30070204 (View on PubMed)

Kobayashi R, Kenji S, Taketomi A, Murakami H, Ono K, Otake H. New mode of burst spinal cord stimulation improved mental status as well as motor function in a patient with Parkinson's disease. Parkinsonism Relat Disord. 2018 Dec;57:82-83. doi: 10.1016/j.parkreldis.2018.07.002. Epub 2018 Jul 6.

Reference Type BACKGROUND
PMID: 30017249 (View on PubMed)

Mazzone P, Viselli F, Ferraina S, Giamundo M, Marano M, Paoloni M, Masedu F, Capozzo A, Scarnati E. High Cervical Spinal Cord Stimulation: A One Year Follow-Up Study on Motor and Non-Motor Functions in Parkinson's Disease. Brain Sci. 2019 Apr 3;9(4):78. doi: 10.3390/brainsci9040078.

Reference Type BACKGROUND
PMID: 30987170 (View on PubMed)

Hubsch C, D'Hardemare V, Ben Maacha M, Ziegler M, Patte-Karsenti N, Thiebaut JB, Gout O, Brandel JP. Tonic spinal cord stimulation as therapeutic option in Parkinson disease with axial symptoms: Effects on walking and quality of life. Parkinsonism Relat Disord. 2019 Jun;63:235-237. doi: 10.1016/j.parkreldis.2019.02.044. Epub 2019 Mar 2.

Reference Type BACKGROUND
PMID: 30852148 (View on PubMed)

Chakravarthy KV, Chaturvedi R, Agari T, Iwamuro H, Reddy R, Matsui A. Single arm prospective multicenter case series on the use of burst stimulation to improve pain and motor symptoms in Parkinson's disease. Bioelectron Med. 2020 Sep 28;6:18. doi: 10.1186/s42234-020-00055-3. eCollection 2020.

Reference Type BACKGROUND
PMID: 33005705 (View on PubMed)

Lai Y, Pan Y, Wang L, Zhang C, Sun B, Li D. Spinal Cord Stimulation with Surgical Lead Improves Pain and Gait in Parkinson's Disease after a Dislocation of Percutaneous Lead: A Case Report. Stereotact Funct Neurosurg. 2020;98(2):104-109. doi: 10.1159/000505707. Epub 2020 Feb 25.

Reference Type BACKGROUND
PMID: 32097953 (View on PubMed)

Prasad S, Aguirre-Padilla DH, Poon YY, Kalsi-Ryan S, Lozano AM, Fasano A. Spinal Cord Stimulation for Very Advanced Parkinson's Disease: A 1-Year Prospective Trial. Mov Disord. 2020 Jun;35(6):1082-1083. doi: 10.1002/mds.28065. Epub 2020 Apr 20. No abstract available.

Reference Type BACKGROUND
PMID: 32311155 (View on PubMed)

Cury RG, Carra RB, Capato TTC, Teixeira MJ, Barbosa ER. Spinal Cord Stimulation for Parkinson's Disease: Dynamic Habituation as a Mechanism of Failure? Mov Disord. 2020 Oct;35(10):1882-1883. doi: 10.1002/mds.28271. No abstract available.

Reference Type BACKGROUND
PMID: 33068473 (View on PubMed)

Samotus O, Parrent A, Jog M. Long-term update of the effect of spinal cord stimulation in advanced Parkinson's disease patients. Brain Stimul. 2020 Sep-Oct;13(5):1196-1197. doi: 10.1016/j.brs.2020.06.004. Epub 2020 Jun 3. No abstract available.

Reference Type BACKGROUND
PMID: 32504828 (View on PubMed)

Reis Menezes J, Bernhart Carra R, Aline Nunes G, da Silva Simoes J, Jacobsen Teixeira M, Paiva Duarte K, Ciampi de Andrade D, Barbosa ER, Antonio Marcolin M, Cury RG. Transcutaneous magnetic spinal cord stimulation for freezing of gait in Parkinson's disease. J Clin Neurosci. 2020 Nov;81:306-309. doi: 10.1016/j.jocn.2020.10.001. Epub 2020 Oct 20.

Reference Type BACKGROUND
PMID: 33222935 (View on PubMed)

Other Identifiers

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SCSPDgait

Identifier Type: -

Identifier Source: org_study_id

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